The article by Yue et al. (1) provides novel insights into the role of IL-21 in HIV infection. Their results are in accord with ours (2) concerning the presence of HIV-specific CD4+ T cells in HIV-infected viremic individuals. However, there is an important point of divergence.

Yue et al. (1) conclude: “HIV-infected individuals had greater circulating IL-21 producing CD4+ T cells in blood as compared with uninfected volunteers.” On the contrary, we have shown decreased frequencies of the cytokine-producing CD4+ T cells in HIV-infected persons compared with those in control subjects. We determined these frequencies in PBMC by flow cytometry after stimulating them with ionomycin for 24 h. In contrast, the stimulus used by Yue et al. (1) is a bacterial superantigen staphylococcal enterotoxin B (SEB) that stimulates only CD4+ T cells bearing TCRs with certain Vβ domains (3). Our unpublished data show that SEB activates only a subset of the ionomycin-stimulated CD4+ T cells. Because humans differ from each other with respect to their repertoires of CD4+ T cells bearing TCRs with different families of Vβ domains, SEB is not an appropriate method to compare the cytokine-producing CD4+ T cell frequencies between control and virus-infected individuals. Should the authors have used a pan-T cell activator, they might have obtained different results. Furthermore, the data shown in Fig. 4B of Yue et al. (1) do not concur with their above mentioned conclusion. Readers of the Yue et al. article (1) should be made aware of these caveats.

1
Yue
F. Y.
,
Lo
C.
,
Sakhdari
A.
,
Lee
E. Y.
,
Kovacs
C. M.
,
Benko
E.
,
Liu
J.
,
Song
H.
,
Jones
R. B.
,
Sheth
P.
, et al
.
2010
.
HIV-specific IL-21 producing CD4+ T cells are induced in acute and chronic progressive HIV infection and are associated with relative viral control
.
J. Immunol.
185
:
498
506
.
2
Iannello
A.
,
Boulassel
M. R.
,
Samarani
S.
,
Debbeche
O.
,
Tremblay
C.
,
Toma
E.
,
Routy
J. P.
,
Ahmad
A.
.
2010
.
Dynamics and consequences of IL-21 production in HIV-infected individuals: a longitudinal and cross-sectional study
.
J. Immunol.
184
:
114
126
.
3
Li
H.
,
Llera
A.
,
Malchiodi
E. L.
,
Mariuzza
R. A.
.
1999
.
The structural basis of T cell activation by superantigens
.
Annu. Rev. Immunol.
17
:
435
466
.